Repair of peripheral nerve injury

Abstract

The invention relates to methods and compositions for maintaining the pro-regenerative capacity of distal nerve segments following nerve injury.

What is claimed is: 
     
       1. A method for maintaining the pro-regenerative capacity of a distal nerve segment subsequent to a nerve injury, the method comprising transplanting a stretch-grown tissue engineered nerve graft (TENG) into a distal site in the distal nerve segment,
 wherein the TENG facilitates axon growth and Schwann cell infiltration, thereby maintaining the pro-regenerative capacity of the distal nerve segment; 
 and wherein the nerve injury occurs as a result of trauma, a surgical procedure, the positioning of a patient during surgery, a compression or crush injury, a disease related to a loss of motor or sensory nerve function, a congenital anomaly, an amputation, complete or partial removal of an organ, tumor or tissue, a metabolic/endocrine complication, inflammatory disease, autoimmune disease, vitamin deficiency, infectious disease, toxin, exposure to organic metal or heavy metal, or administration of a medication or drug. 
 
     
     
       2. The method of  claim 1 , wherein the nerve injury is present in a subject. 
     
     
       3. The method of  claim 2 , wherein the subject is a human. 
     
     
       4. The method of  claim 2 , wherein the subject is a non-human mammal. 
     
     
       5. The method of  claim 1 , wherein the nerve injury comprises an injury to a peripheral nerve of a subject. 
     
     
       6. The method of  claim 1 , wherein the nerve injury comprises an injury to the spinal cord of a subject. 
     
     
       7. The method of  claim 1 , wherein the nerve injury comprises the loss of a segment of nerve. 
     
     
       8. The method of  claim 1 , wherein the nerve injury comprises a nerve lesion of less than about 1 cm in length. 
     
     
       9. The method of  claim 1 , wherein the nerve injury comprises a nerve lesion of at least about 1 cm in length. 
     
     
       10. The method of  claim 1 , wherein the nerve injury comprises a nerve lesion of at least about 3 cm in length. 
     
     
       11. The method of  claim 1 , wherein the nerve injury comprises a nerve lesion of at least 5 cm in length. 
     
     
       12. The method of  claim 1 , wherein the nerve injury comprises multiple nerve lesions. 
     
     
       13. The method of  claim 1 , wherein the pro-regenerative capacity of the distal nerve segment is maintained for at least about 12 weeks. 
     
     
       14. The method of  claim 1 , wherein the pro-regenerative capacity of the distal nerve segment is maintained until at least such time as proximal nerve axons regenerate across the nerve injury. 
     
     
       15. The method of  claim 1 , wherein pro-regenerative capacity of the distal nerve segment is maintained until at least such time as proximal nerve axons reinnervate distal targets. 
     
     
       16. The method of  claim 1 , wherein the method further comprises a primary procedure for nerve repair. 
     
     
       17. The method of  claim 16 , wherein the method results in a greater degree of functional recovery following repair of PNI, as compared to the degree of functional recovery that occurs following the primary procedure alone. 
     
     
       18. The method of  claim 1 , wherein the method is conducted in the absence of any other nerve repair. 
     
     
       19. The method of  claim 1 , further comprising providing a neurotrophic factor, culture supernatant, or cells to the distal nerve segment. 
     
     
       20. The method of  claim 19 , wherein the cells are selected from the group consisting of neurons, and stem cells. 
     
     
       21. The method of  claim 1 , wherein the method does not comprise transecting a nearby healthy nerve or the repaired nerve. 
     
     
       22. The method of  claim 1 , wherein the method enhances the survival of Schwann cells in the distal nerve segment. 
     
     
       23. The method of  claim 1 , wherein the distal site is at least about 3 cm away from the site of injury. 
     
     
       24. The method of  claim 1 , wherein the distal site is less than least about 3 cm away from the site of injury. 
     
     
       25. The method of  claim 1 , wherein the method comprises contacting multiple distal nerve segments with one or more stretch-grown TENG.